Polarization of Tumor-Associated Macrophages Phenotype via Porous Hollow Iron Nanoparticles for Tumor Immunotherapy in vivo
Tumor-associated macrophages (TAMs) are the most important components in tumor immunosuppressive microenvironment, promoting tumor growth and metastasis. Despite TAMs have become to be one of the hot topics of tumor immunotherapy, challenges still remains to achieve TAMs-targeted re-polarization therapy. In this work, porous hollow iron oxide nanoparticles (PHNPs) were synthesized for loading P13K γ small molecule inhibitor (3-Methyladenine,3-MA) and further modified by mannose to target TAMs. The delivery system named PHNPs@DPA-S-S-BSA-MA @3-MA showed good efficiency for targeting TAMs. The inflammatory factor NF-κB p65 of macrophages was activated by the combination of PHNPs and 3-MA, which synergistically switched TAMs to pro-inflammatory M1-type macrophages. As a result, it activated immune responses and inhibited tumor growth in vivo. The study provides an intracellular switch of the TAMs phenotype for targeted TAMs therapy.